Abstract
BackgroundAge, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer.MethodsThis was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium.ResultsThe frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001).ConclusionsAmong the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.
Highlights
Breast cancer begins as a change within mammary epithelial cells that starts them on an estimated 20–30 year course through stages of early precancerous changes, carcinoma in situ, and invasive cancer
In women with premalignant breast changes the frequency of bovine leukemia virus (BLV) DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001)
Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer
Summary
Breast cancer begins as a change within mammary epithelial cells that starts them on an estimated 20–30 year course through stages of early precancerous changes, carcinoma in situ, and invasive cancer. Risk factors for the remaining 90% of cases have been identified, including age, reproductive history, exogenous hormones, diet, exercise, alcohol consumption and other lifestyle factors, the exact agents responsible for the initial cellular/molecular changes are not fully understood. Mouse mammary tumor virus (MMTV), is a retrovirus transmitted from mother to pups via milk [5]. Over the past 50 years there has been considerable interest in determining whether MMTV or a closely related human virus might be transmitted via milk and play an important causative role in human breast cancer. Numerous investigations (1970–1985), found no convincing evidence of an MMTV-like virus in human milk or breast tissues. Reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer
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